B-homo-19-nor-pregnene-3, 20-diones and derivatives thereof



United States Patent Oflice 3,410,872 Patented Nov. 12, 1968 ABSTRACT OFTHE DISCLOSURE Novel B-homo-l9-nor-21unsubstituted-A and Apregnene-3,20-diones and B-homo l9-nor2l-unsubstituted--pregnadiene-3,ZO-diones useful as progestational agents.

This invention relates to novel cyclopentanopolyhydrophenanthrenederivatives and to processes for the preparation thereof.

More particularly, this invention relates to novel B- homo 19 nor 21unsubstituted A and 13 pregnene-3,2 -diones represented by the generalformula:

and also to novel B-homo-18-nor-21 unsubstituted-Apregnadicne-3,20-diones represented by the general formula:

In the above formulas, R represents hydrogen, a hydroxyl group or .anacyloxy group; T represents hydrogen, a-hydroxyl, a-acyloxy, u-methyl orp-methyl; R and T taken together can also represent the grouping:

wherein R represents hydrogen or a lower alkyl group, such as methyl,ethyl, propyl, butyl, or the like and R represents hydrogen, a loweralkyl group, or an aryl (including alkaryl and aralkyl) group containingup to 8 carbon atoms, inclusive, such as phenyl, tolyl, xylyl, benzyl,or the like, and the dotted lines indicate that there is one double bondat either the 4(5 or the 5 10) position.

The acyl and acyloxy groups referred to herein are preferably derivedfrom hydrocarbon carboxylic acids containing less than 12 carbon atomswhich may be saturated or unsaturated, of straight, branched, cyclic orcyclic-aliphatic chain, or aromatic, and may be substituted byfunctional groups such as hydroxy, alkoxy containing up to 5 carbonatoms, acyloxy containing up to 12 carbon atoms, nitro, amino orhalogen. Typical ester groups-are the acetate, propionate, enanthate,benzoate, trimethylacetate, t-butylacetate, phenoxyacetate,cyclopentylpropionate, aminoacetate, and fl-chloropropionate.

The novel B-homo steroids represented by the above formulas areprogestational agents having anti-androgenic, anti-estrogenic,anti-gonadotropic, and diuretic properties. In addition, they can beused in fertility control, in the treatment of premenstrual tension, andin lowering blood cholesterol levels.

One suitable procedure which can be used to prepare the novelB-homo-19-nor-21-unsubstituted-A -pregnene-3, 20-diones represented byFormula A thereinabove can be represented schematically as follows:

CH; i CH: M M I); I M M H l I.

: VIII O 1 VII CH; a, I..... i3 V IX In these formulas R and T have thesame meanings as set forth hereinabove and R represents an acyl group.

In carrying out this procedure the starting material I, aB-homo-19-nor-A -pregnene-3,8,7(a or fi)-diol-20-one 3-acylate, e.g.,B-homo-l9-nor-A -pregnene-3fl,7;8-diol- 20-one 3-acetate (I; R andT:hydrogen, R acetyl), obtained as described in my copending US. patentapplication Ser. No. 423,566, filed Jan. 5, 1965, now abandoned, isfirst ketalized in known manner with a lower alkylene glycol, such asethylene glycol, propylene glycol, or the like, to give thecorresponding ZO-ketal, e.g., B-homo-19- nor 20 cycloethylenedioxy-A-pregnene-3 8,7 8-di0l-3- acetate (II; R and T=hydrogen, R :=acetyl).

Next, the 7-hydroxyl group in this ZO-ketal is oxidized, using chromiumtrioxide in pyridine, or the like, preferably at room temperature (about25 C.) overnight, to give the corresponding 7-keto steroid, e.g.B-homo-19- nor-20-cycloethylenedioxy-A -pregnen 3fl-ol-7-one 3- acetate(III; R and T=hydrogen, R =acetyl).

This 7-keto steroid is then reacted in known manner with a loweralkylene dithiol, such as ethane dithiol, propane dithiol, or the like,to give the corresponding 7- cycloalkylenedithio ketal, e.g.,B-homo-7-cycloethylenedithio-l9-nor-20-cycloethylenedioxy A500)pregnen-3B- o1 3-acetate (IV; R and T=hydrogen, R =acetyl).

The resulting 7-cycloalkylenedithio ketal, dissolved in a lower alkanol,such as methanol, ethanol, or the like, is then refluxed with Raneynickel for from about 8 to about 24 hours, thus producing thecorresponding 7- unsubstituted steroid, e.g., B-homo 19 nor 20cycloethylenedioxy-A -pregnen-3fl-ol 3-acetate (V; R and T=hydrogen, R=acetyl).

Hydrolysis of the 3-acyl group is this 7-unsubstituted steroid, e.g., byrefluxing it in aqueous methanolic potassium hydroxide, gives thecorresponding free 313- hydroxy compound, e.g., B homo 19 nor 20cycloethylenedioxy-A -pregnen-BB-ol (VI; R and T=hydrogen).

Oxidation of the 3-hydroxyl group in the thus-obtained free 3B-hydroxylcompound, using chromium trioxide in pyridine, or the like, in themanner described hereinabove, produces the corresponding 3-keto steroid,e.g., B-homo- 19-nor-20-cycloethylenedioxy-A -pregnen-B-one (VII; R andT=hydrogen) By refluxing the resulting A -3-one with an aqueousmethanolic solution of sodium hydroxide, potassium hydroxide, or thelike, preferably of from about 0.01 N to about 0.1 N, under an inertnitrogen atmosphere, for

4 from about one to about six hours, the double bond can be shifted fromthe 5(10)- to the 4-position without removal of the 20-ketal group, thusgiving, for example, B-homo-19-nor-20-cycloethylenedioxy-M-pregnen 3-one(VIII; R and T:hydrogen).

Preferably, however, th double bond will be shifted at the same time theZO-keto group is regenerated, by dissolving the 20-cycloalkylenedioxy-A-3-one (VII) in an inert organic solvent, preferably a ketone such asacetone, methyl ethyl ketone, methyl isobutyl ketone, or the like, andrefluxing with a strong acid, such as sulfuric acid, hydrochloric acid,p-toluenesulfonic acid, or the like, thus producing the corresponding A-3,20-dione, e.g., B- homo-l9-nor-A -pregnene-3,20-di0ne (IX; R andT=hydrogen), directly. This procedure can also be used to regenerate the20-keto group in the corresponding 20- cycloalkylenedioxy-A -3-one(VIII).

One suitable procedure which can be used to prepare the novel B homo 19nor 21 unsubstituted A pregnene-3,20-diones of Formula A hereinabove andthe novel B-homo-19-nor-21-unsubstituted A pregnadiene-3,20-diones ofFormula B hereinabove can be represented schematically as follows:

("l is l.....;; a; /\l l U I W XIII In these formulas R and T have thesame meanings as set forth hereinabove, X represents chlorine, bromineor iodine and Y represents chlorine or bromine.

In carrying out this procedure the starting material (VI), aB-homo-19-nor 20 cycloalkylenedioxy-A pregnen-3fl-ol, e.g., Bhomo-19-nor20 cycloethylenedioxyA -pregnen-Bfi-ol (VI; R and T=hydrogen), obtainedas described hereinabove, is dissolved in an inert organic solvent andrefluxed with a strong acid, in the same manner described hereinabovefor the regeneration of the 20-keto group in the corresponding20-cycloalkylenedioxy-A -3-one (VII) or -A -3-one (VIII),

5 thus giving the corresponding A -pregnen-3fi-ol-20-one (X; R andT=hydrogen).

Oxidation of the free 3,8-hydroxyl group in the thusobtained A-3B-ol-20-one, using chromium trioxide in pyridine, or the like, in themanner described hereinabove, produces the corresponding A 3,20 dione,e.g., B- homo 19 nor A -pregnene-3,ZO-dione (XI; R and T=hydro gen) ThisA -3,2O-dione is then dihalogenated to produce the corresponding5u,l0B-dihalo steroid, e.g., B-homo-5a,1OB-dibromo-19-norpregnane-3,20-dione (XII; R and T=hydrogen).

Where the halogens introduced at the 5- and lO-positions are the same,i.e., two chlorine atoms or two bromin atoms, the reaction can becarried out as described in U.S. Patent No. 3,086,027 to- Perelman etal., or as described in copending U.S. patent application Ser. No.107,050, filed May 2, 1961, now U.S. Patent 3,139,- 446, using chlorineor bromine in liquid or gaseous form, or any other chlorinating orbrominating agent or chlorine or bromine carrier which liberateschlorine as Cl+, C1 or bromine as Br+, Br, such as N-chloroacetamide orN-chlorosuccinimide together with hydrogen chloride, N-bromoacetamide orN-bromosuccinimide together with hydrogen bromide, trimethylammoniumbromide perbromide, pyridine perbromide hydrobromide, or the like, in anInert organic solvent such as pyridine or a substituted pyridine base,methylene dichloride, carbon tetrachloride, or the like.

Where the halogens introduced at the 5- and l-carbon atoms aredifierent, the reaction will be carried out as described in theaforementioned copending U.S. patent application Ser. No. 107,050, usinga halogen halide, e.g., bromine chloride, iodine chloride, or the like,which can be generated in situ from a mixture of an N-haloamide orN-haloimide, such as N-chlor0-, N-bromoor N-iodoacetamide or N-chloro,'N bromo, or N-iodosuccinimide, or the like, with hydrogen chloride orhydrogen bromide, e.g., mixtures of N-bromoacetamide and hydrogenchloride, N-iodosuccinimide and hydrogen chloride, and the like, in aninert organic solvent, such as one or more of those mentionedhereinabove.

The temperature at which this halogenation reaction is carried out willvary depending on the halogenating agent or halogen carrier used. Thus,where a halogenating agent or halogen carrier other than a mixture of anN-haloamide or -imide and a hydrogen halide is used, the reaction willgenerally be carried out at a temperature of about C. or lower, andpreferably at from about -20 C. to about 0 0, although in certain casestemperatures up to room temperature can be employed. Where thehalogenating agent is a mixture of an N-haloamide or -imide and ahydrogen halide, the reaction will preferably be carried out at atemperature of about 20 C. or less, e.g., temperatures as low as 80 C.can be employed.

The thus-obtained 5a,l0fl-dihalo steroid (XII) is then admixed with apyridine base solvent, such as pyridine itself, collidine, lutidine, orthe like, and reacted at a temperature of about 20 C. to about 30 C. orhigher, and preferably at room temperature, under substantiallyanhydrous conditions, to split out 2 mols of hydrogen halide and givethe corresponding A -diene, e.g., B-homo- 19-nor-A-pregnadiene3,20-dione (XIII; R and T: hydrogen).

In order that those skilled in the art can more fully understand thepresent invention, the following examples are set forth. These examplesare given solely for the purpose of illustrating the invention, andshould not be considered as expressing limitations unless so set forthin the appended claims.

Example I A mixture of 1 gram of B-homo-19-nor-A-pregnene-SfiJfl-diol-ZO-one S-acetate, 25 cc. of anhydrous,thiophene-free benzene, 5 cc. of ethylene glycol and 50 mg. ofp-toluenesulfonic acid monohydrate was refluxed for 16 hours withdistillation of the water formed during the reaction. Following thisreaction period the reaction mixture was washed with an aqueous sodiumbicarbonate solution, then with water, then dried over anhydrous sodiumsulfate, and finally evaporated to dryness. Recrystallization fromacetone/hexane gave B-homo-19-nor-20-cycloethylenedioxy-A-pregnene-3p,7;8-diol 3-actate.

This procedure was then repeated in every detail but one, namely, B-homo19 nor- -pregnene-3fl,7fl-diol- 20-one 3-acetate was replaced by:B-homo-19-nor-A pregnene-3B,7u,17u-triol-20-one 3-acetate,B-hOrnO-16amethyl-l9-nor-A -pregnene-313,7;3-diol-20 one 3 acetate,B-homo-l6fi-methyl-l9-nor-A pregnene 35,70:- diol-20-one 3-acetate,B-homo-l6a-methyl-l9-nor-A pregnene-3fl,7fl,17a-triol-20-one 3-acetate,and B-homo- 16a,17a-isopropylidenedioxy-l9-nor-A pregnene 3,6,7a-diol-20-one 3-acetate.

In each case, the corresponding 20-cycloethylenedioxy steroid, namely,B-homo-l9-nor-20-cycloethylenedioxy- ASOOL regnene-IiBJa,l7u-triol3-acetate, B homo 16amethyl 19-nor-20-cycloethylenedioxy-A-pregnene-Bfi, 7 3 diol 3-acetate, B-homo-l68-methyl-19-nor-20-cycloethylenedioxy-A -pregnene-3fl,7a diol 3 acetate,B- homo 16a methyl 19-nor-20-cycloethylenedioxy-Apregnene-3p,7fi,l7a-triol 3-acetate, and, B homo- 16a, 17aisopropylidenedioxy l9-nor-20-cycloethylenedioxy- A-pregnene-3fl,7ot-diol 3-acetate, respectively, was obtained.

Example II A solution of 6 grams ofB-homo-19-nor-20-cycloethylenedioxy-A -pregnene-ZiflJfi-diol 3-acetatein cc. of pyridine was added to a mixture of 6 grams of chromiumtrioxide in 120 cc. of pyridine, and the resulting reaction mixture wasthen allowed to stand at room temperature (25 C.) overnight. Followingthis reaction period the reaction mixture was diluted with ethyl acetateand then filtered through Celite. The resulting filtrate was washedthoroughly with water, then dried over anhydrous sodium sulfate andevaporated to dryness. Crystallization from acetone/hexane gaveB-homo-19-nor-20-cycloethylenedioxy-A -pregnen-3 9-ol-7-one 3-acetate.

By repeating this procedure in every detail but one, namely, replacingB-horno-19-nor-20-cycloethylenedioxy- A -pregnene-SflJfl-diol 3-acetatewith the remaining ZO-cycloethylenedioxy steroids prepared as describedin Example I hereinabove, the corresponding 7-ones, namely, B-homo 19nor-20-cycloethylenedioxy-A -pregnene- 35,17u-diol-7-one S-acetate,B-homo-16a-methyl-19-nor- 20 cycloethylenedioxy A-pregn-ene-3fi-O1-7-0ne 3- acetate, B homo 16Bmethyl-l9-nor-20-cycloethylenedioxy A500) pregnen-3,3-ol-7-one3-acetate, B-homo- 16a methyl 19 nor 20-cycloethylenedioxy-Apregnene-SB,l7a-diol-7-one 3-acetate, and B-h0m0-16a, 17aisopropylidenedioxy l9-nor-20-cycloethylenedioxy- A500) pregnen3fi-ol-7-One S-acetate, respectively, were obtained.

Example III dried over anhydrous sodium sulfate and finally evaporatedto dryness. Recrystallization from diethyl ether/ hexane gaveB-homo-l9-nor-7-cycloethylenedithio-ZO-cyc1oethylenedioxy-A-pregnen-3p-ol 3-acetate.

This. procedure was then repeated in every detail with one exception,namely, B-homo-19-nor-20-cycloethylenedioxy A pregnen-3fi-ol-7-one3-acetate was replaced by the remaining 7-ones obtained as described inExample II hereinabove. In each case, the corresponding7-cycloethylenedithio derivative, namely, B-homo-7-cycloethylenedithio19 nor 2O-cycloethylenedioxy-A pregnene-3fi,l7ot-diol 3-acetate,B-homo-7-cycloethylenedithio-l6ot-methyl-19-nor 20 cycloethylenedioxy-Apregnen-3,B ol 3-acetate, B-homo-7-cycloethylenedithio- 16,8 methyl19-nor-20-cycloethylenedioxy-A -pregnen 3fi-ol 3-acetate,B-homo-7-cycloethylenedithio-16amethyl-19-nor-ZO-cycloethylenedioxyA500) pregnene- 3,8,l7a-diol 3-acetate, andB-homo-7-cycloethylenedithio- 16a,17u-isopropylidenedioxy-19-norcycloethylenedioxy-A -pregnen-3,8-ol 3-acetate, respectively, wereobtained.

Example IV A solution of 4 grams of B-homo-7-cycloethylenedithio 19 nor20 cycloethylenedioxy A pregnen-3 3-ol 3-acetate in 3 liters of ethanol(previously distilled from Raney nickel), containing 50 grams of Raneynickel, was refluxed for 6 hours. Following this reaction period thereaction mixture was filtered to remove the Raney nickel, which was thenwashed with hot ethanol and the washings added to the filtrate. Thecombined ethanol solution was then evaporated to dryness, and theresulting residue was dissolved in chloroform. This chloroform solutionwas washed with dilute hydrochloric acid, then with aqueous sodiumcarbonate solution and finally with water. The solution was then driedover anhydrous sodium sulfate and evaporated to dryness. Crystallizationof the thus-obtained residue from acetone/hexane gave B homo l9 nor 20cycloethylenedioxy 43 pregnen-Bfl-ol 3-acetate.

By repeating this procedure in every detail but one, namely, replacingB-homo-7-cycloethylenedithio-l9'nor- 20-cycloethylenedioxy-A-pregnen-3B-o1 3-acetate with the remaining 7-cycloethylenedithioderivatives prepared as described in Example III hereinabove, thecorresponding 7-unsubstituted steroids, namely, B-homo-19-nor-20-cycloethylenedioxy A -pregnene-3fl,l7vt-diol 3-acetate, B homo 16amethyl 19 nor-20-cycloethylenedioxy- A -pregnen-3/3-ol 3-acetate,B-homo-16 8-methyl-19- nor-2O-cycloethylenedioxy-A -pregnen-3B-ol3-acetate, B homo 16a methyl 19 nor 20 cycloethylenedioxy A500)pregnene-3,3,l7a-diol 3-acetate, and B-homo- 16u,l7uisopropylidenedioxy-19-nor-20-cycloethylenedioxy-A -pregnen-3[3013-acetate, respectively, were obtained.

Example V A solution of 1 gram of B-homo-19-nor-20-cycloethylenedioxy-A-pregnen-3,8-ol 3-acetate in 50 cc. of methanol was admixed with asolution of 500 mg. of potassium hydroxide in 1 cc. of water, and theresulting reaction mixture was refluxed for three hours. Following thisreaction period, the reaction mixture was poured into ice water, and theresulting precipitate was collected by filtration, washed with wateruntil neutral, and dried. Recrystallization of the thus-obtained crudematerial from methylene dichloride/diethyl ether gave B-homo-19-nor-20-cycloethylenedioxy-A -pregnen-3;3-ol.

This procedure was then repeated with one exception, namely, -B homo 19nor-2O-cycloethylenedioxy-A pregnen-3fi-ol 3-acetate was replaced by theremaining B-acetates of Example IV hereinabove. In each case, thecorresponding free -01, namely, B-homo-19-nor-20- cycloethylenedioxy A-pregnene-3fl,17ot-diol, B-homo- 16a methyl 19 nor 20 cycloethylenedioxyA pregnen-3fl-ol, B-homo-lop-methyl-l9-nor-20-cycloethylenedioxy Apregnen 3p ol, B-homo-16a-methyl-19- nor 20 cycloethylenedioxy Apregnene 315?,l7ocdiol, andB-homo-l6a,l7a-isopropylidenedioxy-l9-nor-2U- cycloethylenedioxy A500)pregnen-3p 01, respectively, were obtained.

8 Example VI B homo 19 nor 20 cycloethylenedioxy A pregnen-3fl-ol wasoxidized, using chromium trioxide in pyridine, in the manner describedin Example II hereinabove, thus givingB-homo-19-nor-20-cycloethylenedioxy- A -pregnen-3-one.

By repeating this procedure using the remaining free 3B-0ls prepared asdescribed in Example V hereinabove as the steroid starting materials,the corresponding 3- ones, namely, B-homo-l9-nor-20-cyeloethylenedioxy-A -pregnen-l7ot-ol-3-one, B-homo-l6a-methyl-l9-nor-20-cycloethylenedioxy-A -pregnen-3-one, B-homo-l6,8- methyl l9 nor 20cycloethylenedioxy A pregnen 3 one, Bhomo-l6ot-methyl-l9-nor-20-cycloethylenedioxy-A -pregnen-17a-0l-3-one,and B-homo-16ot- 17a isopropylidenedioxy l9 nor 20 cycloethylenedi0xy-A-pregnen-3-one respectively, were obtained.

Example VII A solution of 2 grams ofB-horno-l9nor-20-cycloethylenedioxy-A -pregnen-3-one in 70 cc. ofmethanol containing 7 ml. of aqueous 8% sulfuric acid was refluxed for40 minutes. Following this reaction period the reaction mixture wasneutralized by the addition of aqueous saturated sodium carbonatesolution, then concentrated to about 20 ml. under vacuum and poured intowater. The thus-formed precipitate was collected by filtration andwashed thoroughly with water. Recrystallization from acetone gaveB-hom0-19-nor-A pregnene-3,20- dione.

By repeating this procedure using the remaining 3-ones prepared asdescribed in Example VI hereinabove, as the steroid starting materials,the corresponding A -3,20- diones, namely, B-homo-l9-nor-A-pregnenl7tx-ol-3,20- dione, B homo 16a methyl l9-nor-A -pregnene-3,20-dione, B homo methyl 19-nor-A -pregnene-3,20- dione, Bhomo-16a-methyl-19-nor-A -pregnen-l7ix-ol-3, 20-dione, andB-homo-l6a,I7a-isopropylidenedi0xy-l9- nor-A -pregnen-3,20-di0ne,respectively, were obtained.

Example VIII B homo l9 nor 20 cycloethylenedioxy A pregnen-3B-ol wasrefluxed with sulfuric acid in methanol in the manner described inExample VII hereinabove to give B-homo-19-nor-A -pregnen-3fi-ol-2O-one.

By repeating this procedure using the remaining 20- cycloethylenedioxy-3B-ols prepared as described in Example V hereinabove, the corresponding3 8-ol20-0nes, namely, B homo 19-nor-A -pregnene-3B,17a-diol-20- one, Bhomo-16a-rnethyl-l9-nor-A -pregnen-3;3-ol-20 one, Bhomo-16B-n1ethyl-l9-nor-A -pregnen-3/3-ol-20- one, B 16a methyl l9 norA500) pregnene 35, 17a diol 20 one, and,B-homo-l6u,l7a-isopropylidenedioxy-l9-nor-A -pregnen-3[3-ol,respectively, were obtained.

Example IX B homo 19-nor-A -pregnen-3fi-ol-20-one was oxidized, usingchromium trioxide in pyridine, in the manner described in Example IIhereinabove, to give B-homo- 19-n0r-A -pregnene-3,20-dione.

This procedure was then repeated in every detail but one, namely, theremaining 3/8-ol-20-ones prepared as described in Example VIIIhereinabove were used as the steroid starting materials. In each case,the corresponding 3,20-dione, namely, B-homo-19-n0r-A pregnen-17a-ol-3,20-dione, B-hOIIlO-16(1-II16ihy1-19-I1OFA -pI6gnene-3,20-dione, B-homo-16,8-methyl-l9-nor-A -pregnen-l7a-ol-3,20-dione,and B-homo-16a,17ot-isopropylidenedioxy-19-nor-A -pregnene-3,20-dione,respectively, were obtained.

Example X To a solution of 2.5 grams of B-homo-19-nor-A pregnene 3,20dione in 25 cc. of methylene dichloride,

maintained at --5 C., there was added dropwise over a 30 minute period,with stirring, a solution of 2 grams of bromine in 25 cc. of methylenedichloride. The resulting reaction mixture was allowed to stand at C.for minutes, then poured into an aqueous 5% sodium bicar- 5 bonatesolution and extracted with methylene dichloride. The thus-obtainedextract was washed with water, dried over anhydrous sodium sulfate andevaporated to dryness. Crystallization from acetone/hexane gave B-homo-5a,10fi-dibromo-19 nor-pregnane-3,20-dione. By repeating this procedurein every detail but one, namely, using the remaining 3,20-dionesprepared as described in Example IX hereinabove, the corresponding 5a,10fl-dibromo steroids, namely,

B-homo-5a,1OB-dibromo-19-nor-pregnan-17a-0l-3,20-

dione,

B-homo-5a,10 8-dibromo-16m-methyl-19-nor-pregnane- 3,20-dione,

B-homo-S 11,10fi-dibl'01110- 16/3-methyl-19-nor-pregnane- 3,20-dione,

B-hOmo-Sa,1(ifi-dibromo-l6u-methyl-l9-nor-pregnan- 17a-ol-3,20-dione,and

B-homo-5a,IOfi-dibromo-l611,17a-isopropylidenedioxy-10-nor-pregnane-3,20-dione,

respectively, were obtained.

Example XI One gram of B-hQmo-Sa,10,8-dibromo-19-nor-pregnane-3,20-dione was dissolved in 100 mg. of anhydrous, redistilled pyridine,and the resulting reaction mixture was then allowed to stand at roomtemperature, with stirring overnight. Following this reaction period thereaction mixture was diluted with water and extracted with methylenedichloride/diethyl ether (1:1 by volume). The resulting extract waswashed successively with 1 N hydrochloric acid, an aqueous l-N sodiumhydroxide solution, and then with water until neutral. Next, the neutralsolution was dried over anhydrous sodium sulfate and evaporated todryness under vacuum. Recrystallization from acetone gaveB-homo-19-nor-A -pregnadiene-3,20- dione.

This procedure was then repeated in every detail but one, namely,B-homo-5a,1OB-dibromo-l9-nor-pregnane- 3,20-dione was replaced by theremaining 5a,10fi-dibromo intermediates prepared as described in ExampleX hereinabove. In each case, the corresponding A -diene, namely,

B-homo-19-nor-A -pregnadiene-17u-ol 3,20-dione,

B-homo-16a-methyl-19-nor-A -pregnadiene-3,20-

dione,

B-homo-16B-methyl-19-nor-A -pregnadiene-3,20

dione,

B-hom0-16a-methyl-19-nor-A -pregnadien-17a-0l- 3,20-dione, and

B-homo-16a,17u-isopr0pylidene-l9-nor-A -pregnadiene-3,20-dione,

respectively, was obtained.

It will be obvious to those skilled in the art that other changes andvariations can be made in carrying out the 60 present invention withoutdeparting from the spirit and scope thereof as defined in the appendedclaims.

I claim:

1. A compound represented by the formula:

wherein R is selected from the group consisting of hydrogen, hydroxyland a hydrocarbon carboxylic acyloxy group containing less than 12carbon atoms; T is selected from the group consisting of hydrogen,a-hydroxyl, ahydrocarbon carboxylic acyloxy containing less than 12carbon atoms, a-methyl and fl-rnethyl; and R and T taken togetherrepresent the grouping:

wherein R is selected from the group consisting of hydrogen and loweralkyl and R is selected from the group consisting, of hydrogen, loweralkyl, and aryl containing up to 8 carbon atoms, inclusive.

2. B-homo-19 nor-A -pregnene-3,20-dione.

3. B-homo-19-nor-A -pregnen-17a-ol-3,20-dione. 4.B-homo-1Gar-methyl-19-nor-A -pregnene-3,20- dione.

5. B-homo-1li-methyl-l9-nor-A -pregnene-3,20- dione.

6. B-homo-l6u-methyl-19-nor-A -pregnen-1711-01 3,20-dione.

7. B-homo-16u,l7a-isopropylidenedioxy-19-nor-A pregnene-3,20-dione.

8. A compound represented by the formula:

wherein R is selected from the group consisting of hydrogen, hydroxyland a hydrocarbon carboxylic acyloxy group containing less than 12carbon atoms; T is selected from the group consisting of hydrogen,a-hydroxyl, ahydrocarbon carboxylic acyloxy containing less than 12carbon atoms, a-methyl and fl-methyl; and R and T taken togetherrepresent the grouping:

wherein R is selected from the group consisting of hydrogen and loweralkyl and R is selected from the group consisting of hydrogen, loweralkyl, and aryl containing up to 8 carbon atoms, inclusive.

9. B-homo-19-nor-A -pregnene-3,20-dionelf 10. B-homo-19-nor-A-pregnen-17a-ol--3,20-dione.

11. B-homo-16a-methyl-19-nor-A -pregnene-3,20-dione.

12. B-homo-l6fi-methyl-19-nor-A -pregnene-3,20 dione.

13. B-homo-16wmethyl-19-nor-A -pregnen-17a-ol-3,20- dione.

14. B homo 16a,17a-isopropyliden.edioxy-19-nor-A pregnene-3,20-dione.

15. A compound represented by the formula:

wherein R is selected from the group consisting of hydrogen, hydroxy anda hydrocarbon carboxylic acyloxy group containing less than 12 carbonatoms; T is selected from 1 1 the group consisting of hydrogen,a-hydroxyl, a-hydrocarbon carboxylic acyloxy containing less than 12carbon atoms, a-methyl and B-methyl, and R and T taken togetherrepresent the grouping:

wherein R is selected from the group consisting of hydrogen and loweralkyl and R is selected from the group consisting of hydrogen, loweralkyl, and aryl containing up to 8 carbon atoms, inclusive.

16. B-homo-19-nor-A -pregnadiene-3,ZO-dione.

17. B homo 19-nor-A -pregnadien-17a-ol-3,20- dione.

18. B homo 16a-methyl-19-norA -pregnadiene- 3,20-dione.

12 19. B homo 16fl-methy1-19-nor-A -pregnadiene- 3,20-dione.

20. B-horno-16a-methyl-19-nor-A pregnadien-17aol-3,20-dione.

21. B-homo 16a,17a isopropylidenedioxy 19 nor- A-pregn=adiene-3,20-dione.

References Cited UNITED STATES PATENTS 6/1964 Muller et a1. 260-488OTHER REFERENCES Carpio et :11.: Journal of Organic Chemistry, vol. 30(12), 1965, pp. 4154-59.

NICHOLAS S. RIZZO, Primary Examiner.

J. H. TURNIPSEED, Assistant Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No.3,410,872 November 12, 1968 John A. Edwards It is certified that errorappears in the above identified patent and that said Letters Patent arehereby corrected as shown below:

Column 1, line 38, "l8-nor" should read l9-nor Column 2, that portion offormula II reading "R C" should read R 0- Column 8, line 53, "B-loashould read B-homo-l6a line 69, "nen-17u-ol-3,ZO-dione" should readnene3,20-dione, Bhomo- 16u-methyll9nor'-A pregnen17a-o1-3,ZO-dioneColumn 9, line 24, "10-nor" should read 19*nor Signed and sealed thisIOthday of March 1970.

(SEAL) Attest:

WILLIAM E. SCHUYLER, JR.

Commissioner of Patents Edward M. Fletcher, Jr. Attesting Officer

